Single Dose Oral and Intravenous Pharmacokinetics and Tissue Distribution of a Novel Hesperetin Derivative MTBH in Rats.

BACKGROUND

MTBH, a novel hesperetin derivative, possesses in vivo hepatoprotective effects against carbon tetrachloride (CCl4)-induced acute liver injury in Institute of Cancer Research (ICR) mice.

OBJECTIVES

This study investigated the pharmacokinetics and tissue distribution of MTBH and its conjugated metabolites in rats after a single dose of MTBH.

METHODS

Male Sprague-Dawley (SD) rats were orally administered (25, 50, 100 mg/kg) or intravenously administered (25 mg/kg) MTBH and blood samples were withdrawn at specific times. Moreover, after a single oral dose of MTBH (200 mg/kg), tissues (heart, liver, spleen, lung, kidney, stomach, intestine, brain and muscle) were collected at scheduled time points.

RESULTS

The concentration of MTBH in plasma and tissues was assayed by HPLC before and after hydrolysis with β-glucuronidase or sulfatase. The glucuronides/sulfates were extensively present in the plasma, moreover, the free form was detectable in the plasma, but in a small amount equivalent to nearly 0.85-1.46 % of the amount of glucuronides/sulfates, the absolute bioavailability of MTBH was approximately 31.27 %. In tissues, the free form appeared in all tissues examined, with trace amount in brain and muscle, and considerable concentration in stomach and lung. Glucuronides/sulfates were the major forms in intestine, kidney and liver, whereas not detectable in heart, brain and muscle. The liver and intestine were found likely to accumulate MTBH at a high concentration among all tissues.

CONCLUSIONS

The free form of MTBH was present in the circulation and all assayed organs, whereas its glucuronides/sulfates were the major forms in plasma and intestine, kidney and liver after a single dose.